Platelets and extracellular vesicles in cancer: diagnostic
and therapeutic implications
Springer Science+Business Media, LLC, part of Springer Nature 2018
Several pieces of evidence support the role of activated platelets in the development of the chronic inflammation-related diseases,
such as atherothrombosis and cancer, mainly via the release of soluble factors and microparticles (MPs). Platelets and MPs
contain a repertoire of proteins and genetic material (i.e., mRNAs and microRNAs) which may be influenced by the clinical
condition of the individuals. In fact, platelets are capable of up-taking proteins and genetic material during their lifespan.
Moreover, the content of platelet-derived MPs can be delivered to other cells, including stromal, immune, epithelial, and cancer
cells, to change their phenotype and functions, thus contributing to cancer promotion and its metastasization. Platelets and MPs
can play an indirect role in the metastatic process by helping malignant cells to escape from immunological surveillance.
Furthermore, platelets and their derived MPs represent a potential source for blood biomarker development in oncology. This
review provides an updated overview of the roles played by platelets and MPs in cancer and metastasis formation. The possible
analysis of platelet and MP molecular signatures for the detection of cancer and monitoring of anticancer treatments is discussed.
Finally, the potential use of MPs as vectors for drug delivery systems to cancer cells is put forward.
Numerous pieces of evidence convincingly support the con-
tribution of platelets in cancer development and progression.
The first clue comes from the observation that the use of the
antiplatelet agent low-dose aspirin is associated with reduced
incidence and mortality for colorectal cancer (CRC) and other
types of cancer [1, 2]. Importantly, aspirin was found to pre-
vent the risk of distant metastasis [3–5]. These findings open
the way to perform a large number of studies to clarify the
possible mechanisms of aspirin action. Based on the preferen-
tial action on the platelet by aspirin when administered at low
doses, once daily, it was hypothesized that the antiplatelet
effect of the drug might play a central role in the protection
against cancer [6–9]. This idea was the driving force to study
in detail how platelets may contribute to tumorigenesis and
metastasis. The results of these studies uncovered novel
biological roles of platelets beyond hemostasis and thrombo-
sis. Interestingly, it was also discovered that the assessment of
platelet content (including RNAs and proteins) describes spe-
cific signatures that give information on cancer diagnosis and
In this review, we report the clinical and experimental ev-
idence sustaining the role of platelets and their released prod-
ucts (soluble mediators and vesicles) in the development of
cancer, its malignant progression leading to tumor cell spread-
ing to other distant organs. Finally, the possible evaluation of
platelets and their microparticle (MP) molecular signatures for
the detection of cancer and monitoring of anticancer treat-
ments is discussed.
1 Clinical evidence of the role played
by platelets in cancer
The evidence that daily low-dose aspirin may help combat
cancer derives from the results of observational case-control
studies and their meta-analysis [5, 13], meta-analysis from
randomized controlled trials (RCTs) in subjects with sporadic
colorectal adenomas , an RCT in Lynch syndrome patients
with a post-trial follow-up [15, 16], and a meta-analysis of
Melania Dovizio and Annalisa Bruno contributed equally to this work.
* Paola Patrignani
Department of Neuroscience, Imaging and Clinical Sciences and
Center for Research on Aging and Translational Medicine
(CeSI-MeT), Systems Pharmacology Laboratory, BG. d’Annunzio^
University, Chieti, Italy
Cancer and Metastasis Reviews